6 ms·

I don't know much about this, but wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly vi

I don't know much about this, but wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections?

rzzzt 7mo ago
Me neither, but I got something similar from the abstract that I was about to ask, so adding it here: "Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung." That latter term (ectopic lymphoid structure) comes up in connection with persistent inflammation where the immune system sets up camp near the problem point. Is this good or bad? Do these go away once the infection clears up?
- dillydogg 7mo ago
  These are pretty common, physiologic structures associated with infections. They can be just a handful of cells on a slide or be quite large, and I don't know what they found in these infections. I didn't read the original paper. The ectopic lymphoid structures go away after the infection resolves. It seems that the immune system has ways to set up mini lymph node architecture right by the site of infections, which is very sensible. The same process is going on in a more organized way in the draining lymph node in parallel. Research into these was really hot in the 2010s, but people don't seem to be as into them anymore (but my research has also transitioned to innate immunity from adaptive, so it's likely that I'm no longer in that universe). In general, it doesn't surprise me that when you prime the innate immune system, the adaptive immune system works well. The problem is that pathogens have an incredible suite of tools ready to evade these mechanisms. The doses of the pathogens are typically insanely high too, which I do not think model natural infections well. Anyways, this is intriguing, so I'll take a look at the original paper one of these days. Vaccine research generally is so boring. It's like, we vaccinated, and it worked, or didn't, no mechanism.
ivan_gammel 7mo ago
Or worse. If it is so easy to activate, there must be an evolutionary reason why we don’t have it.
- MarkusQ 7mo ago
  Systemic cost. We could have paper shredders, blenders, toasters, water taps, and so on that just ran all the time, but our utility bills would be ginormous. Same thing for our bodies.
  - lokar 7mo ago
    Or the risk of autoimmune disease?
    - ekianjo 7mo ago
      Yes that's the obvious one
    - MarkusQ 7mo ago
      Yep. And probably increased allergies. Possibly decreased fertility. And who knows what else.
- Rexxar 7mo ago
  Maybe it would made the immune system age faster if it is "used" too much.
  - ekianjo 7mo ago
    Inflammation is certainly not "free". It causes systemic damage.
    - tensor 7mo ago
      So does getting infected over and over. Much worse damage. Evolution isn't some magic thing that gives you the most optimal creature for a given metric. The only metric is procreation. Not longevity. Not a pleasant life.
MathMonkeyMan 7mo ago
Yep! But you are also a mouse who has limited venues in which to complain. I wonder if the vaccine causes inflammatory and other unpleasant responses when administered. If so, I wonder if those responses go away after the last dose, when the three months of protection begin. Here are the two paragraphs that I found interesting: > The new vaccine, for now known as GLA-3M-052-LS+OVA, mimics the T cell signals that directly stimulate innate immune cells in the lungs. It also contains a harmless antigen, an egg protein called ovalbumin or OVA, which recruits T cells into the lungs to maintain the innate response for weeks to months. > In the study, mice were given a drop of the vaccine in their noses. Some recieved multiple doses, given a week apart. Each mouse was then exposed to one type of respiratory virus. With three doses of the vaccine, mice were protected against SARS-CoV-2 and other coronaviruses for at least three months.
- Terr_ 7mo ago
  > It also contains a harmless antigen, an egg protein called ovalbumin or OVA Here's hoping the final product doesn't have a side-effect of inducing an allergy to the main component of egg-whites. Although even if that happened... Would it only apply to the raw materials, as opposed to cooked products where the ovalbumin was denatured by heat? Edit: No, wait! What about "safe to eat" cookie-dough, which uses heat-treated flour and pasteurized eggs as ingredients!? The might still have intact ovalbumin, and obviously I can't give it up.
  - shiroiuma 7mo ago
    And what about people who eat actual raw egg? I routinely eat freshly-made cake batter (made with raw eggs; I just clean the bowl, I don't actually gobble tons of raw cake batter), for instance. It's perfectly safe because I live in a country where they actually check eggs for salmonella before selling them and people routinely eat raw eggs on top of things.
    - kuerbel 7mo ago
      Raw flour is just as dangerous. It can contain e coli and salmonella, among other bacteria.
Animats 7mo ago
Right, that's been mentioned elsewhere. A new area of research has opened up. This approach may be more useful for treatment than prevention. It's not really a vaccine; it's more like an induced vaccine response. Keeping the immune system in that state full time might be a problem. But after an infection, that's what's wanted.
- rossdavidh 7mo ago
  I think that "vaccine" is really not the right word to use for this; they sound as different as bandages and blood transfusions. But if it works as advertised, it could be useful if used in the right situation. I do wonder if the kind of people who got vaccinated 10 times against Covid-19 will end up trying to get a sniff of this every month? Kind of like how we overuse antibiotics in cleaners. It seems like it would be best if saved for an "oh shoot" kind of situation.
  - xattt 7mo ago
    Inoculation?
- ipaddr 7mo ago
  Some autoimmune diseases are a result of an immune system always on.
standardUser 7mo ago
People with severe allergies or at high risk would probably make the tradeoff even if side effects were a problem. If they're not a problem, I could see most people taking this regularly just to avoid the nuisance of respiratory infections.
infinitewars 7mo ago
Yes, I've had exactly this ever since my first COVID experience. If I come across anyone with even a tiny level of COVID or flu, it sets of inflammation in my lungs within minutes. Haven't gotten sick in six years now but this inflammation has happened probably one hundred times and is indeed quite unpleasant.
shiroiuma 7mo ago
>wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections? It might be worth it, at least during certain times of the year. For much of the winter, for instance, I already seem to have a lot of nasal drainage and other unpleasant symptoms for the whole time, along with the occasional actual infection which is much more unpleasant. There's certain times when there's big flare-ups of infections such as flu, so maybe giving everyone an annoying vaccine during that time which gives them the sniffles would actually improve things overall.
modeless 7mo ago
The tradeoff might not be something unpleasant. For example, it might be that the immune system uses a lot more energy in this state, which would be bad for survival in the wild with limited resources but probably harmless or even beneficial for modern humans with abundant food.

rzzzt 7mo ago

Me neither, but I got something similar from the abstract that I was about to ask, so adding it here: "Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung." That latter term (ectopic lymphoid structure) comes up in connection with persistent inflammation where the immune system sets up camp near the problem point. Is this good or bad? Do these go away once the infection clears up?

dillydogg 7mo ago
These are pretty common, physiologic structures associated with infections. They can be just a handful of cells on a slide or be quite large, and I don't know what they found in these infections. I didn't read the original paper. The ectopic lymphoid structures go away after the infection resolves. It seems that the immune system has ways to set up mini lymph node architecture right by the site of infections, which is very sensible. The same process is going on in a more organized way in the draining lymph node in parallel. Research into these was really hot in the 2010s, but people don't seem to be as into them anymore (but my research has also transitioned to innate immunity from adaptive, so it's likely that I'm no longer in that universe). In general, it doesn't surprise me that when you prime the innate immune system, the adaptive immune system works well. The problem is that pathogens have an incredible suite of tools ready to evade these mechanisms. The doses of the pathogens are typically insanely high too, which I do not think model natural infections well. Anyways, this is intriguing, so I'll take a look at the original paper one of these days. Vaccine research generally is so boring. It's like, we vaccinated, and it worked, or didn't, no mechanism.

ivan_gammel 7mo ago

Or worse. If it is so easy to activate, there must be an evolutionary reason why we don’t have it.

MarkusQ 7mo ago
Systemic cost. We could have paper shredders, blenders, toasters, water taps, and so on that just ran all the time, but our utility bills would be ginormous. Same thing for our bodies.
- lokar 7mo ago
  Or the risk of autoimmune disease?
  - ekianjo 7mo ago
    Yes that's the obvious one
  - MarkusQ 7mo ago
    Yep. And probably increased allergies. Possibly decreased fertility. And who knows what else.
Rexxar 7mo ago
Maybe it would made the immune system age faster if it is "used" too much.
- ekianjo 7mo ago
  Inflammation is certainly not "free". It causes systemic damage.
  - tensor 7mo ago
    So does getting infected over and over. Much worse damage. Evolution isn't some magic thing that gives you the most optimal creature for a given metric. The only metric is procreation. Not longevity. Not a pleasant life.

MathMonkeyMan 7mo ago

Yep! But you are also a mouse who has limited venues in which to complain. I wonder if the vaccine causes inflammatory and other unpleasant responses when administered. If so, I wonder if those responses go away after the last dose, when the three months of protection begin. Here are the two paragraphs that I found interesting: > The new vaccine, for now known as GLA-3M-052-LS+OVA, mimics the T cell signals that directly stimulate innate immune cells in the lungs. It also contains a harmless antigen, an egg protein called ovalbumin or OVA, which recruits T cells into the lungs to maintain the innate response for weeks to months. > In the study, mice were given a drop of the vaccine in their noses. Some recieved multiple doses, given a week apart. Each mouse was then exposed to one type of respiratory virus. With three doses of the vaccine, mice were protected against SARS-CoV-2 and other coronaviruses for at least three months.

Terr_ 7mo ago
> It also contains a harmless antigen, an egg protein called ovalbumin or OVA Here's hoping the final product doesn't have a side-effect of inducing an allergy to the main component of egg-whites. Although even if that happened... Would it only apply to the raw materials, as opposed to cooked products where the ovalbumin was denatured by heat? Edit: No, wait! What about "safe to eat" cookie-dough, which uses heat-treated flour and pasteurized eggs as ingredients!? The might still have intact ovalbumin, and obviously I can't give it up.
- shiroiuma 7mo ago
  And what about people who eat actual raw egg? I routinely eat freshly-made cake batter (made with raw eggs; I just clean the bowl, I don't actually gobble tons of raw cake batter), for instance. It's perfectly safe because I live in a country where they actually check eggs for salmonella before selling them and people routinely eat raw eggs on top of things.
  - kuerbel 7mo ago
    Raw flour is just as dangerous. It can contain e coli and salmonella, among other bacteria.

Animats 7mo ago

Right, that's been mentioned elsewhere. A new area of research has opened up. This approach may be more useful for treatment than prevention. It's not really a vaccine; it's more like an induced vaccine response. Keeping the immune system in that state full time might be a problem. But after an infection, that's what's wanted.

rossdavidh 7mo ago
I think that "vaccine" is really not the right word to use for this; they sound as different as bandages and blood transfusions. But if it works as advertised, it could be useful if used in the right situation. I do wonder if the kind of people who got vaccinated 10 times against Covid-19 will end up trying to get a sniff of this every month? Kind of like how we overuse antibiotics in cleaners. It seems like it would be best if saved for an "oh shoot" kind of situation.
- xattt 7mo ago
  Inoculation?
ipaddr 7mo ago
Some autoimmune diseases are a result of an immune system always on.

standardUser 7mo ago

People with severe allergies or at high risk would probably make the tradeoff even if side effects were a problem. If they're not a problem, I could see most people taking this regularly just to avoid the nuisance of respiratory infections.

infinitewars 7mo ago

Yes, I've had exactly this ever since my first COVID experience. If I come across anyone with even a tiny level of COVID or flu, it sets of inflammation in my lungs within minutes. Haven't gotten sick in six years now but this inflammation has happened probably one hundred times and is indeed quite unpleasant.

shiroiuma 7mo ago

>wouldn't the description of this imply you're stimulating the body to be in an a long-term situation that would be commonly viewed as unpleasant (inflamed, maybe nasal drainage, that type of thing) with the positive tradeoff that you get fewer actual infections? It might be worth it, at least during certain times of the year. For much of the winter, for instance, I already seem to have a lot of nasal drainage and other unpleasant symptoms for the whole time, along with the occasional actual infection which is much more unpleasant. There's certain times when there's big flare-ups of infections such as flu, so maybe giving everyone an annoying vaccine during that time which gives them the sniffles would actually improve things overall.

modeless 7mo ago

The tradeoff might not be something unpleasant. For example, it might be that the immune system uses a lot more energy in this state, which would be bad for survival in the wild with limited resources but probably harmless or even beneficial for modern humans with abundant food.